Wen Z-Q, Li S-H, Shui X, Tang L-L, Zheng J-R, Chen L
Department of Cardiovascular Medicine, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Eur Rev Med Pharmacol Sci. 2019 Aug;23(3 Suppl):281-286. doi: 10.26355/eurrev_201908_18658.
To uncover the role of long non-coding RNA (lncRNA) PEG10 in the progression of cardiac hypertrophy by regulating HOXA9.
In vivo cardiac hypertrophy model was established by performing transverse aortic constriction model (TAC) procedures in mice. Relative levels of PEG10, ANP and BNP in mice undergoing TAC procedures or sham operations were determined. In vitro cardiac hypertrophy model was established by phenylephrine (PE) treatment in primary cardiomyocytes. Relative levels of PEG10, ANP and BNP in cardiomyocytes were determined as well. Regulatory effects of HOXA9 on surface area of cardiomyocytes and relative levels of ANP and BNP were assessed. Finally, potential influences of PEG10/HOXA9 regulatory loop on cell surface area and relative levels of ANP and BNP were explored.
Compared with mice in sham group, those in TAC group presented higher levels of PEG10, ANP and BNP. PE treatment markedly upregulated PEG10, ANP and BNP in primary cardiomyocytes, which were downregulated by transfection of si-PEG10. Besides, surface area of cardiomyocytes was enlarged by PE treatment, which was reduced after silence of PEG10. Silence of HOXA9 presented a similar effect as that of PEG10 in cardiomyocytes. Transfection of si-HOXA9 reversed the expanded cell surface area, and upregulated ANP and BNP in cardiomyocytes overexpressing PEG10.
PEG10 is upregulated in hypertrophic cardiomyocytes. PEG10 aggravates cardiac hypertrophy by positively regulating HOXA9.
通过调控HOXA9揭示长链非编码RNA（lncRNA）PEG10在心肌肥厚进展中的作用。
通过对小鼠进行主动脉缩窄模型（TAC）建立体内心肌肥厚模型。测定接受TAC手术或假手术的小鼠中PEG10、心钠素（ANP）和脑钠肽（BNP）的相对水平。通过用去甲肾上腺素（PE）处理原代心肌细胞建立体外心肌肥厚模型。同时测定心肌细胞中PEG10、ANP和BNP的相对水平。评估HOXA9对心肌细胞表面积以及ANP和BNP相对水平的调节作用。最后，探究PEG10/HOXA9调控环对细胞表面积以及ANP和BNP相对水平的潜在影响。
与假手术组小鼠相比，TAC组小鼠的PEG10、ANP和BNP水平更高。PE处理显著上调原代心肌细胞中的PEG10、ANP和BNP，而转染si-PEG10可使其下调。此外，PE处理使心肌细胞表面积增大，沉默PEG10后表面积减小。沉默HOXA9在心肌细胞中呈现出与PEG10类似的效果。转染si-HOXA9可逆转过表达PEG10的心肌细胞中扩大的细胞表面积，并上调ANP和BNP。
PEG10在肥厚型心肌细胞中上调。PEG10通过正向调控HOXA9加重心肌肥厚。
